Thursday, June 19, 2014
Aldehyde dehydrogenase (ALDH);
proto-oncogene (MET; HGFR); epidermal growth factor receptor 1
Cell culture and mouse
studies suggest ALDH inhibitors could help treat cancer. In human cancer cell
lines expressing MET or EGFR1, the acquisition of resistance to inhibitors
was associated with upregulation of ALDH. In multiple kinase-dependent cancer
cell lines, an ALDH inhibitor plus an inhibitor of the respective kinase
increased cell death compared with either agent alone. In mice bearing
EGFR1-dependent xenograft lung tumors, an ALDH inhibitor plus an EGFR1
inhibitor decreased tumor growth and increased time to tumor recurrence
compared with an EGFR1 inhibitor alone. Ongoing work includes testing ALDH
inhibitors in mouse models of other cancers.
Pharmaceuticals Corp. has TKM-ALDH2,
an siRNA targeting aldehyde
dehydrogenase 2 family mitochondrial (ALDH2)
formulated using lipid nanoparticle delivery technology, in preclinical
testing to treat addiction.
Published online June 19, 2014
Patent and licensing status
Raha, D. et al. Cancer
published online May 8, 2014;
Contact: Jeff Settleman, Genentech Inc.,
San Francisco, Calif.
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